Molecular and cellular morphology of placenta unveils new mechanisms of reproductive immunology

作者：Penghao Li, Liting Zeng, Xiaomiao Yan, Ziqi Zhu, Qinlan Gu, Xuqing He, Sujuan Zhang, Rurong Mao, Jingliang Xu, Fengshan Xie, Hui Wang, Ziteng Li, Jing Shu, Weifeng Zhang, Yulin Sha, Jin Huang, Meng Su, Qu Zheng, Jian Ma, Xiaolin Zhou, Ming Li, Pan Haiying, Ya Li, Meiling Yan, Xueling Chen, Mingzhou Li, Keren Long, Fanli Kong, Chuang Tang, Ju Huang, Chanjuan Su, Jirui Li, Zheng Fang, Mu‐Wang Chen, Erpo Tian, Ying Zhong, Jiang Gu · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.01.025 · 被引用次数：3 · 研究领域：Reproductive System and Pregnancy、Pregnancy and preeclampsia studies、Preterm Birth and Chorioamnionitis

INTRODUCTION: Despite of numerous studies of the placenta, some molecular and cellular characteristics, particularly the relationship among different cell types, have not been well understood. We aim to investigate the basic and intricate details of cellular and molecular elements in early and late phase placentas to gain better understanding of the immune regulation of human reproductive process. METHODS: A novel combination of techniques of spatial transcriptomics(ST), multiple immunohistochemistry, and a dual labeling combining immunohistochemistry and (fluorescence in situ hybridization) FISH on normal and ectopic pregnancy and animal models was employed to investigate the placenta at tissue, cell, protein and molecular levels and to trace the fetal and maternal origin of every cell in early and late placentas. RESULTS: Original discoveries include early expression of immune checkpoint proteins in embryo trophoblasts even before implantation. The detailed distributional relationships among different cell types of fetal and maternal origins in placenta and decidua indicate an immune rejection of the mother towards the fetus and this was counterbalanced by immune inhibitory proteins and blocking antibody Immunoglobulin G4 (IgG4) at the junction between the fetus and the mother. In contrary to common believe, we found that vascular endothelial and glandular epithelial cells in the decidua remain maternal in origin and were not replaced by fetal cells. At term placenta, fetal...